Girling R, Partridge J F, Bandara L R, Burden N, Totty N F, Hsuan J J, La Thangue N B
Laboratory of Eukaryotic Molecular Genetics, MRC National Institute for Medical Research, Mill Hill, London, UK.
Nature. 1993 Mar 4;362(6415):83-7. doi: 10.1038/362083a0.
Transcription factor DRTF1/E2F coordinates events in the cell cycle with transcription by its cyclical interactions with important regulators of cellular proliferation like the retinoblastoma tumour-suppressor gene product (Rb) and the Rb-related protein, p107 (refs 1-8). DRTF1/E2F binding sites occur in the control regions of genes involved in proliferation, and both Rb and p107 repress the capacity of DRTF1/E2F to activate transcription (refs 11, 12; M. Zamanian and N.B.L.T., manuscript submitted). Mutant Rb proteins isolated from tumour cells are unable to bind DRTF1/E2F (refs 11-13), and certain viral oncoproteins, such as adenovirus E1A, sequester Rb and p107 in order to free active DRTF1/E2F (refs 5, 11, 12, 14, 15). Here we report the isolation of a complementary DNA encoding DRTF1-polypeptide-1 (DP-1), a major sequence-specific binding protein that is present in DRTF1/E2F, including Rb- and p107-associated DRTF1/E2F. The DNA-binding domain of DP-1 contains a region that resembles that of E2F-1 (refs 16, 17), and recognizes the same sequence. DRTF1/E2F thus appears to contain at least two sequence-specific DNA-binding proteins.
转录因子DRTF1/E2F通过与细胞增殖的重要调节因子(如视网膜母细胞瘤肿瘤抑制基因产物(Rb)和Rb相关蛋白p107)的周期性相互作用,将细胞周期中的事件与转录过程协调起来(参考文献1 - 8)。DRTF1/E2F结合位点存在于参与增殖的基因的控制区域,Rb和p107都能抑制DRTF1/E2F激活转录的能力(参考文献11、12;M. Zamanian和N.B.L.T.,待发表手稿)。从肿瘤细胞中分离出的突变型Rb蛋白无法与DRTF1/E2F结合(参考文献11 - 13),某些病毒癌蛋白,如腺病毒E1A,会隔离Rb和p107以释放活性DRTF1/E2F(参考文献5、11、12、14、15)。在此,我们报告了一种互补DNA的分离,该DNA编码DRTF1 - 多肽 - 1(DP - 1),它是DRTF1/E2F中的一种主要序列特异性结合蛋白,包括与Rb和p107相关的DRTF1/E2F。DP - 1的DNA结合结构域包含一个与E2F - 1相似的区域(参考文献16、17),并识别相同的序列。因此,DRTF1/E2F似乎至少包含两种序列特异性DNA结合蛋白。